Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways
| Autor: | Joel Leborgne, Férial Toumi, Jean-Paul Galmiche, Michel Neunlist, Christian L. Laboisse, Marc G. Denis, Anne Jarry, Tsvetelina Oreschkova |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Cell Survival Colon Physiology Vasoactive intestinal peptide Biology Cell junction Enteric Nervous System Permeability Cell Line Tight Junctions Intestinal mucosa Culture Techniques Physiology (medical) medicine Humans Intestinal Mucosa Aged Aged 80 and over Hepatology Tight junction Gastroenterology Membrane Proteins Middle Aged Phosphoproteins Coculture Techniques Electric Stimulation Cell biology medicine.anatomical_structure Caco-2 Paracellular transport Zonula Occludens-1 Protein Female Enteric nervous system Neuron Caco-2 Cells Vasoactive Intestinal Peptide |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 285:G1028-G1036 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00066.2003 |
| Popis: | Although the enteric nervous system (ENS) has been shown to regulate various mucosal functions, its role in the physiological control of the human intestinal epithelial barrier is unknown. The aim of this study was to investigate whether the ENS is able to modulate epithelial barrier permeability and a key tight junction-associated protein, zonula occludens-1 (ZO-1). Therefore, we developed a co-culture model, consisting of human submucosa containing the submucosal neuronal network and human polarized colonic epithelial monolayers (HT29-Cl.16E or Caco-2). Submucosal neurons were activated by electrical field stimulation (EFS). Permeability was assessed by measuring the flux of paracellular permeability markers (FITC-dextran or FITC-inulin) across epithelial monolayers. Expression of ZO-1 was determined by immunofluorescence, quantitative immunoblot analysis, and real time RT-PCR. Using the coculture model, we showed that EFS of submucosal neurons resulted in a reduction in FITC-dextran or FITC-inulin fluxes, which was blocked by TTX. In HT29-Cl.16E, the effect of submucosal neuron activation was blocked by a VIP receptor antagonist (VIPra) and reproduced by VIP. Furthermore, ZO-1 expression (mRNA, protein) assessed in HT29-Cl.16E, was significantly increased after submucosal neuron activation by EFS. These effects on ZO-1 expression were blocked by TTX and VIPra and reproduced by VIP. In conclusion, our results strongly suggest a modulatory role of VIPergic submucosal neuronal pathways on intestinal epithelial barrier permeability and ZO-1 expression. |
| Databáze: | OpenAIRE |
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